细胞外基质(PCM)是各种组织类型中常驻细胞周围的直接微细胞,调节矩阵周转,细胞-基质串扰和疾病启动。这项研究阐明了纤维软骨中PCM的结构机械性能和机械生物学功能,一个结缔组织家族,在体内承受复杂的拉伸和压缩载荷。研究鼠半月板作为模型组织,我们发现纤维软骨含有较薄的PCM,捕获蛋白聚糖的随机胶原纤维网络,一种不同于密集堆积的结构,大量细胞外基质(ECM)中的胶原纤维高度对齐。与ECM相比,PCM具有较低的模量和较大的各向同性,但相对粘弹性相似。在Col5a1+/D半月板中,胶原蛋白V的减少,定位于PCM中的少量胶原蛋白,导致异常原纤维增厚,异质性增加。因此,PCM表现出降低的模量,各向同性的损失和更快的粘弹性松弛。这种破坏的PCM有助于干扰驻留半月板细胞的机械转导,如细胞内钙信号减少所示,以及上调赖氨酰氧化酶和生腱蛋白C的生物合成。Col5a1+/D半月板细胞合成了一个弱化的新生PCM,在保护常驻细胞免受施加的拉伸拉伸方面具有较差的性能。这些发现强调了PCM作为一个独特的微观结构,控制纤维软骨力学生物学,并强调了胶原蛋白V在PCM功能中的关键作用。靶向PCM或其分子成分不仅有望增强半月板再生和骨关节炎干预,而且还解决了各种纤维软骨组织的疾病。
The pericellular matrix (PCM) is the immediate microniche surrounding resident cells in various tissue types, regulating matrix turnover, cell-matrix cross-talk and disease initiation. This study elucidated the structure-mechanical properties and mechanobiological functions of the PCM in
fibrocartilage, a family of connective tissues that sustain complex tensile and compressive loads in vivo. Studying the murine meniscus as the model tissue, we showed that
fibrocartilage PCM contains thinner, random collagen fibrillar networks that entrap proteoglycans, a structure distinct from the densely packed, highly aligned collagen fibers in the bulk extracellular matrix (ECM). In comparison to the ECM, the PCM has a lower modulus and greater isotropy, but similar relative viscoelastic properties. In Col5a1 +/- menisci, the reduction of collagen V, a minor collagen localized in the PCM, resulted in aberrant fibril thickening with increased heterogeneity. Consequently, the PCM exhibited a reduced modulus, loss of isotropy and faster viscoelastic relaxation. This disrupted PCM contributes to perturbed mechanotransduction of resident meniscal cells, as illustrated by reduced intracellular calcium signaling, as well as upregulated biosynthesis of lysyl oxidase and tenascin C. When cultured in vitro, Col5a1 +/- meniscal cells synthesized a weakened nascent PCM, which had inferior properties towards protecting resident cells against applied tensile stretch. These findings underscore the PCM as a distinctive microstructure that governs
fibrocartilage mechanobiology, and highlight the pivotal role of collagen V in PCM function. Targeting the PCM or its molecular constituents holds promise for enhancing not only meniscus regeneration and osteoarthritis intervention, but also addressing diseases across various fibrocartilaginous tissues.